A TRP Channel Senses Lysosome Neutralization by Pathogens to Trigger Their Expulsion

Cell. 2015 Jun 4;161(6):1306-19. doi: 10.1016/j.cell.2015.05.009. Epub 2015 May 28.


Vertebrate cells have evolved elaborate cell-autonomous defense programs to monitor subcellular compartments for infection and to evoke counter-responses. These programs are activated by pathogen-associated pattern molecules and by various strategies intracellular pathogens employ to alter cellular microenvironments. Here, we show that, when uropathogenic E. coli (UPEC) infect bladder epithelial cells (BECs), they are targeted by autophagy but avoid degradation because of their capacity to neutralize lysosomal pH. This change is detected by mucolipin TRP channel 3 (TRPML3), a transient receptor potential cation channel localized to lysosomes. TRPML3 activation then spontaneously initiates lysosome exocytosis, resulting in expulsion of exosome-encased bacteria. These studies reveal a cellular default system for lysosome homeostasis that has been co-opted by the autonomous defense program to clear recalcitrant pathogens.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autophagy
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / microbiology
  • Escherichia coli Infections / pathology
  • Exocytosis
  • Lysosomes / enzymology
  • Lysosomes / metabolism
  • Lysosomes / microbiology*
  • Mice
  • TRPC Cation Channels / metabolism*
  • Transient Receptor Potential Channels / metabolism*
  • Urinary Bladder / immunology
  • Urinary Bladder / microbiology
  • Urinary Bladder / pathology
  • Urinary Tract Infections / immunology*
  • Urinary Tract Infections / microbiology
  • Urinary Tract Infections / pathology
  • Uropathogenic Escherichia coli / physiology*


  • Mcoln3 protein, mouse
  • TRPC Cation Channels
  • Transient Receptor Potential Channels
  • transient receptor potential cation channel, subfamily C, member 1